Gastric Cancer-Derived Extracellular Vesicles (EVs) Promote Angiogenesis via Angiopoietin-2

Angiogenesis is an important control point of gastric cancer (GC) progression and metastasis. Angiopoietin-2 (ANG2) is a key driver of tumor angiogenesis and metastasis, and it has been identified in primary GC tissues. Extracellular vesicles (EVs) play an important role in mediating intercellular communication through the transfer of proteins between cells. However, the expression of ANG2 in GC-EVs has never been reported. Here, we characterized the EV-mediated crosstalk between GC and endothelial cells (ECs), with particular focus on the role of ANG2. We first demonstrate that ANG2 is expressed in GC primary and metastatic tissues. We then isolated EVs from two different GC cell lines and showed that these EVs enhance EC proliferation, migration, invasion, and tube formation in vitro and in vivo. Using an angiogenesis protein array, we showed that GC-EVs contain high levels of proangiogenic proteins, including ANG2. Lastly, using Lenti viral ANG2-shRNA, we demonstrated that the proangiogenic effects of the GC-EVs were mediated by ANG2 through the activation of the PI3K/Akt signal transduction pathway. Our data suggest a new mechanism via which GC cells induce angiogenesis. This knowledge may be utilized to develop new therapies in gastric cancer

Patterns of Long COVID Symptoms: A Multi-Center Cross Sectional Study

Background: Long COVID has become a burden on healthcare systems worldwide. Research into the etiology and risk factors has been impeded by observing all diverse manifestations as part of a single entity. We aimed to determine patterns of symptoms in convalescing COVID-19 patients. Methods: Symptomatic patients were recruited from four countries. Data were collected regarding demographics, comorbidities, acute disease and persistent symptoms. Factor analysis was performed to elucidate symptom patterns. Associations of the patterns with patients’ characteristics, features of acute disease and effect on daily life were sought. Results: We included 1027 symptomatic post-COVID individuals in the analysis. The majority of participants were graded as having a non-severe acute COVID-19 (N = 763, 74.3%). We identified six patterns of symptoms: cognitive, pain-syndrome, pulmonary, cardiac, anosmia-dysgeusia and headache. The cognitive pattern was the major symptoms pattern, explaining 26.2% of the variance; the other patterns each explained 6.5–9.5% of the variance. The cognitive pattern was higher in patients who were outpatients during the acute disease. The pain-syndrome pattern was associated with acute disease severity, higher in women and increased with age. The pulmonary pattern was associated with prior lung disease and severe acute disease. Only two of the patterns (cognitive and cardiac) were associated with failure to return to pre-COVID occupational and physical activity status. Conclusion: Long COVID diverse symptoms can be grouped into six unique patterns. Using these patterns in future research may improve our understanding of pathophysiology and risk factors of persistent COVID, provide homogenous terminology for clinical research, and direct therapeutic interventions